Cannabinoid use generalizes stress responses by altering the astrocyte plasticity through extracellular matrix signaling in the nucleus accumbens core.
Research square August 21, 2025 Ritchy Hodebourg, Lillian Duncan, Eric Dereschewitz et al.
Cannabinoid use after stress causes male rats to generalize fear responses to neutral cues and adopt avoidant coping behaviors. The combination of THC and CBD triggered distinct brain changes in the nucleus accumbens core: astrocytes retracted from synapses and Synapsin-I density decreased when a neutral odor was presented, while exposure to a stress-conditioned odor activated MMP-2,9 (mostly MMP-2), re-associated astrocytes to synapses, increased Synapsin-I density, and caused astrocyte atrophy. These neuroadaptations occurred only in males. The findings suggest MMPs and astrocytes as potential therapeutic targets for co-occurring cannabis use disorder and PTSD.